Study identifies signs and symptoms of colorectal cancer risk at younger ages
Authors: Mike Fillon
Journal: CA A Cancer Journal for Clinicians (2023)

“The overarching objective [of this study] is to improve the early detection of CRC at younger ages, which holds significant potential for improving patient outcomes.”—Yin Cao, ScD, MPH Eight years ago, Paula Chambers-Raney from Houston, Texas, suffered from stomach pain, blood in her stool, and anemia. Her primary care physician told her that she had hemorrhoids. Then, over the next 18 months, other clinicians told her that she might have irritable bowel syndrome, she had probably eaten something red, and she should eat more green leafy vegetables for her anemia. After losing her job because of the number of sick days she had taken, with her health still not improving, she went to her county hospital’s emergency room for a colonoscopy. “They found a baseball-sized tumor,” says Chambers-Raney. “I was 44 years old and up until then was told I was too young to have something serious like colon cancer.” Recognizing the alarming trend of younger people being diagnosed with colorectal cancer (CRC), in 2018, the American Cancer Society, followed by other health organizations, began recommending lowering the age for screening from the age of 50 years to the age of 45 years. A new study appearing in the Journal of the National Cancer Institute (doi:10.1093/jnci/djad068) is the latest to validate this change. In the study, the researchers looked for abdominal pain, rectal bleeding, diarrhea, and iron-deficiency anemia, with each indicating an increased risk for early-onset CRC. They sought to determine if these four symptoms—identified as red flags—might be key to the detection of early-onset CRC. To perform this work, the researchers conducted a nested case-control study from the IBM MarketScan Commercial Database, which includes individual claims data from approximately 113 million insured adults aged 18–64 years from across the United States. The primary analyses were restricted to adults aged 18–49 years with at least 2 years of continuous enrollment before the index date. For the secondary analyses, they included adults aged 50–64 years. Four “red-flag” signs and symptoms with an onset 3 months to 2 years before the diagnosis of colorectal cancer (CRC) were identified: abdominal pain, rectal bleeding, diarrhea, and iron-deficiency anemia. Although 19.3% of people ultimately diagnosed with CRC had their first CRC symptoms within this timeframe, an additional 49.1% became symptomatic within 3 months of their diagnosis. The primary analyses focused on identifying red-flag indications that appeared 3 months to 2 years before the index date of diagnosis. “Ultimately, the overarching objective is to improve the early detection of CRC at younger ages, which holds significant potential for improving patient outcomes,” says senior study author Yin Cao, ScD, MPH, an associate professor of surgery in the Division of Public Health Sciences of the Department of Surgery at Washington University School of Medicine in St. Louis, Missouri. “To our knowledge, this study is among the first large-scale studies to identify predictive red-flag signs and symptoms for early-onset CRC compared to a matched control group and in comparison with signs and symptoms in people with CRC diagnosed at older ages,” she says. The researchers found that 19.3% of people with early-onset CRC had symptoms beginning within 3 months to 2 years of their diagnosis with a median diagnostic interval of 8.7 months. In addition, 49.1% first showed symptoms within 3 months of their diagnosis. Also, the median diagnostic interval appeared quickly—less than 1 month—for patients who had their first red-flag sign or symptom within the 3 months before their diagnosis. Having one, two, or three or more red-flag signs and symptoms within 3 months to 2 years of the date of diagnosis was associated with a 1.9-, 3.6-, or 6.5-fold increased risk, respectively. Abdominal pain was associated with a 34% higher risk of early-onset CRC; it was present in 11.6% of patients with CRC within 3 months to 2 years of the date of diagnosis but in only 7.7% in the control group. Although not as common, rectal bleeding was associated with the highest odds for early-onset CRC (7.2% of patients with CRC vs. 1.3% in the control group). The combination of these four signs and symptoms was associated with an 18% increased risk of early-onset CRC as early as 18 months before the date of diagnosis. Dr Cao notes that despite recent adjustments to screening guidelines, which now recommend screening from the age of 45 years, approximately half of all early-onset CRC cases are diagnosed before the age of 45 years. “As the majority of people with early-onset CRC have been and will continue to be diagnosed after symptom presentation, there exists a pressing and unaddressed clinical need to identify potential red-flag signs and symptoms that can facilitate early detection. Yet, our knowledge of signs and symptoms, especially preceding the typical workup for early-onset CRC, is thus far limited.” “I do find the study informative, and it adds to the literature in regard to overall risk if a patient has one, two or three or greater symptoms,” says Cathy Eng, MD, professor of medicine, the David H. Johnson Chair in Surgical and Medical Oncology, and codirector of gastrointestinal oncology at Vanderbilt University Medical Center in Nashville, Tennessee. “However, I think these data do have limitations and need to be recognized for that in regard to early diagnosis and relative risk.” Dr Eng has concerns that a large chunk of potential data is being excluded. “I worry that we’re missing out on an important patient population,” she says. “Specifically, many young people don’t have their own insurance and, of course, there are other socioeconomic issues leading to disparities in an insurance database; as a result, many would not be included in the data. They’re also presuming the patients are documenting everything. I don’t think we should presume that.” Dr Cao says that it is crucial for clinicians to raise awareness among primary care physicians, gastroenterologists, emergency medicine physicians, and other clinical specialties regarding the impact of CRC among younger adults and the prevalent issue of diagnostic delays. “By ensuring that medical practitioners across various disciplines are knowledgeable about this pressing concern and the alarming signs and symptoms associated with early-onset colorectal cancer, they can facilitate prompt and appropriate evaluation for younger adults presenting with potential indicators of the disease,” she says. Dr Cao also recommends that cancer researchers tackle the growing burden of early-onset CRC. “It is essential to broaden the scope of research priorities beyond the investigation of risk factors that contribute to its rising incidence.” Of particular significance, she says, is the urgent need to prioritize research endeavors aimed at improving early detection. “It is essential to develop strategies and interventions that are accessible, culturally sensitive, and considerate of socioeconomic factors. By taking a comprehensive and inclusive approach, we can maximize the impact of our efforts and ensure that the benefits of early detection extend to individuals from various backgrounds and communities.” Dr Eng says that studies that bring greater awareness of this burgeoning problem are helpful: “I guess, in the past, clinicians just ruled it out or didn’t take it as a strong possibility, but now they should be more aware, that these could in fact be symptoms of colorectal cancer. “Personally, I would like screening to begin earlier than age 45, but I am a bit biased because that’s the patient population that I see quite frequently in my clinic,” she adds. “But I hope that, with increased recognition, hopefully we will be able to identify patients earlier who have an earlier stage of presentation, and that will bring increased recognition to the [importance of] reducing the age to even lower than 45.” Only after her tumor was removed did Chambers-Raney learn that she was genetically predisposed to having CRC. The good news is that she has had no evidence of the disease for 5 years. “If these guidelines had been in place, it would have saved me a lot of pain and fear,” said Chambers-Raney, who is now a CRC screening advocate for the American Cancer Society. “I think it’s important for all clinicians to adopt these guidelines. Patients should also include them in their own personal toolboxes.” For more information on the American Cancer Society guidelines, visit https://acsjournals.onlinelibrary.wiley.com/doi/full/10.3322/caac.21457.